Mycoplasma gallisepticum belongs to the class Mollicutes. It causes chronic respiratory disease in avian species. M. gallisepticum is characterized by lack of cell wall; reduced genome size and the volume of its nucleoid is comparable to the size of the whole cell. As a result of genome reduction, M. gallisepticum has a limited variety of DNA-binding proteins (DBP) and transcription factors. It was shown, however, that mycoplasmas demonstrate a wide range of differential expression in response to various stress factors, which promotes effective adaptation to unfavorable conditions. We assume that in the case of mycoplasmas, which are characterized by a combination of the reduction of known gene expression regulation systems and a high adaptive potential, the coordination of gene expression can be provided due to local changes in the structure and spatial organization of the chromosome. The study of the dynamic changes of the proteomic profile of M. gallisepticum nucleoid may assist in revealing its mechanisms of functioning, regulation of chromosome organization and stress adaptation including its changes upon invasion of the host cells.